- Welcome to "Healthy Minds."

I'm Dr. Jeff Borenstein.

Everyone is touched by psychiatric conditions either themselves or a loved one.

Do not suffer in silence, with help, there is hope.

Today on "Healthy Minds"....

Welcome to "Healthy Minds."

I'm Dr. Jeff Borenstein.

Today I speak with Dr. Maura Boldrini about her research on the effect of COVID on the brain.

What do you need to know about psychiatric symptoms, such as anxiety and depression, which may occur as a result of COVID, and how can you treat those symptoms?

That's today, on "Healthy Minds."

(gentle music) This program is brought to you in part by the American Psychiatric Association Foundation, The Bank of America Charitable Gift Fund and The John and Polly Sparks Foundation.

Maura, thank you for joining us today.

- Thank you, Jeff, for having me.

- I wanna jump in and ask you to describe, the research that you've been doing about the effect of COVID on the brain.

- Yes, so during the pandemic we had been involved as psychiatrists to see people with COVID, because they presented with symptoms that we were used to see in people with psychiatric disorders.

Like hallucinations, paranoia, depression and we have heard of cases that ended up dying by suicide after contracting COVID.

So we became very, very curious and interested in what was going on.

And we had been studying the role of inflammation in psychiatric conditions like suicide and depression.

And so we put two and two together and said, "I think it's worth looking in the brain what's happening in people who died."

And at Columbia University, we started collecting tissue at autopsy from unfortunately people who died from COVID and in many cases, the brain was collected as well.

And we started looking in brain areas that could have been involved in the kind of symptoms we were seeing.

And we started seeing increased inflammation, increased activation of microglia, they are these cells involved in housekeeping when inflammation is going on.

And also we start now measuring neurons and cells and we start seeing fewer of neurons that we are used to see in normal brains to be there and proliferating.

- So what you're seeing are the effects that COVID had on the brain, above and beyond the stress of having COVID, direct effects on the brain, that can cause some of these psychiatric symptoms that you described.

- Yes.

- How does COVID do this?

Does COVID go into the brain?

Is it due to inflammation as a result of the COVID?

What's the mechanism of action for this?

- Yeah, so, a few studies have investigated if the virus actually penetrates into the brain.

And there could be possible ways that this could happen.

So through the nose, the virus can penetrate and has been found in the olfactory areas, and in the olfactory bulb in the brain.

And then from there could migrate back in other areas of the brain.

Also, there are some places in the brain where we don't have vascular protection from entrance of the brain.

And that's what we call the blood-brain barrier which is a barrier that protects the brain from what's circulating in our blood.

There are some places where this blood-brain barrier is not there because the brain needs to sense, when there are toxic agents in our blood.

Like for instance, when you have been intoxicated with food poisoning, you wanna make sure you can throw up.

So, the brain make us vomit when there is something like that.

So in these little areas the blood brain barrier is not there, and there are other places where there is both vulnerability from the virus to enter.

Now studies that has found the virus irony, are saying that there isn't a lot of penetration and it doesn't go very far into the gray matter.

On the other hand, we know that, when there is elevated inflammatory levels like you were mentioning, this blood-brain barrier can be disrupted throughout the system.

And so inflammatory markers can penetrate in the brain and activate a whole cascade of changes that can affect the way neurons work.

- So in one of the areas that you've studied has to do with inflammation of the brain prior to COVID but inflammation of the brain and how that could relate to depression or suicide risk, etc.

So this has been an area of study even before COVID existed?

- Yes, in 2014, I got a grant from the BBRF or previously NARSAD, to study inflammation in the hippocampus in people who died by suicide and had depression.

Because we knew that people with depression had elevated in inflammatory markers, even in the blood, and we started looking in the brain and we are very interested in the hippocampus because has an important role in memory, and also in emotional responses to stress.

And is a region where we know now that there is the potential for neurons to regenerate.

We found stem cells in the hippocampus.

It's a very controversial field in the human literature.

But in mice or monkeys, we know that this region of the brain makes new neurons throughout life.

And we detect that in human as well.

And we then said, "Well if there is alterations at these levels there could be producing symptoms that we see in depression and people who die by suicide.

And depression involves changes not just in emotional regulation, but also memory."

So yes, we started looking at the neurons that are proliferating in this area that has neurogenic potential.

And we found so far that in the COVID brain tissue there was about 10 times fewer of these new neurons that we see in normally aging people.

- So we now know that older brains can grow new brain cells.

When I went to medical school, I was taught old brains cannot grow new cells, and old was after the age of two.

And we now that older brains can grow.

We now know older brains can grow new cells.

And one of the findings that you that you've observed is that in these brains affected by COVID, less of that is happening.

And that may impart account for some of the symptoms that people with COVID may have experienced.

- Yes, we have been, like I said, like you.

When I was in medical school they were teaching us that the brain does not proliferate.

And at some point during my postdoc, I noticed the studies that were starting to show that this was happening in rodents.

And I wanted to study this in human brain.

So we started looking in our brain collection here at Columbia University and evaluating people of different ages that were dying from sudden causes, and so the brain was very well preserved.

And also people that didn't have drug of abuse or other medications on board that could affect what we could see.

And yes, indeed we found using the same markers that were used in the mouse work, and also markers that are used often to detect cancer cells that are proliferating.

We detected these markers in this region of the brain, in the hippocampus neurogenic niche, which is an area where vasculature and neurons interact very closely when these stem cells are growing and differentiating slowly into neurons.

- I wanna ask you about the scope of the problem in terms of the effect of COVID on the brain.

Is there a sense of the percentage of people that are affected in terms of brain symptoms when they develop COVID?

- Yes, so some studies in Europe have investigated post COVID people and trying to understand how many of them were still presenting with insomnia, depression, fatigue, or cognitive symptoms like difficulty concentrating, the famous brain fog.

And they had detected that variable percentage of these symptoms from 30% to even 70%.

And we have a clinic here that is following up people right now post COVID, to understand what's the percentage that has these different brain symptoms.

And even according to their data, it seems like at least 30 to 40% have depressive symptoms or insomnia.

Of course, we don't know exactly what are the mechanisms of this.

And potentially we would have to study brains in vivo meaning study people that are still alive with brain imaging, looking for inflammatory markers that we could do with PET, positron emission tomography, using radio traces that detect inflammatory molecules in the brain.

And also investigate this way specific brain regions, which is what we try to do, we're trying to do in the postmortem brain.

Now we have a grant that has been funded by the National Institute of Allergy and Infectious Diseases.

And we are going to look at these inflammatory markers and also do gene sequencing for RNA sequencing, for not just the virus but also other are genes that could be involved in this inflammatory response.

Looking at different regions, specifically the region's responsible for the symptoms we were observing.

And we believe that the prolonged inflammation is what may be causing the problem.

When inflammation goes beyond the time that is actually sort of needed for responding to the virus.

- If someone is experiencing those symptoms, anxiety depression, insomnia, the brain fog.

After recovering from the physical sequela of COVID, what should they do?

- There are centers that are specifically working on that.

And we have groups at Columbia and Cornell that they are following up people that are neurologists and psychiatrists that are interested in the neuro psychiatric presentations of COVID.

We have been treating people with the medications that we normally use for depression, and also the people presenting with psychosis or hallucination, they have been treated with agents that target the serotonergic system.

And they have been able to a achieve remission of these symptoms.

And this is not something we do just based on the symptom but because we know that when there is increased inflammation, there is a deviation of the pathway that makes a serotonin, that goes in a different direction.

So serotonin becomes lacking in the system.

And that's how we think we can help reestablish the levels that are needed.

- So if somebody post COVID is experiencing depression for example, they should seek help.

And some of the antidepressants that have the serotonergic effects that you are responding to, can be effective for them just as they could be effective somebody with depression, unrelated to COVID?

- Yes, and like I said we now starting to see more and more, the connection between depression unrelated to COVID in which we found increased inflammatory markers, and this kind of depression.

So at this point, the two things are sort of coming together.

On the other hand, there could be the potential to identify agents that target the inflammatory response more directly that might have a role in this kind of presentations.

And actually we knew even from other inflammatory diseases that this increase inflammation can affect the brain.

Like many autoimmune diseases like lupus and others, have presentations that involve the brain.

So we knew something about this, but on the other hand this COVID pandemic, maybe the silver line is that we are gonna learn much more about the brain than we knew before.

- It's always good to find some silver lining in something that's a tragedy, but it may help us learn more.

Is there yet information about the role of being vaccinated?

We know that the vaccine can be protective from potentially getting COVID, or if a person gets COVID with the vaccine, from having a severe case of COVID.

- Yeah.

- Do we have information yet about how that plays into the inflammation and the potential brain sequela from a COVID infection?

- Yes, look, I would say that it's careful to say that since with vaccination, we don't get a severe disease.

The immediate response that we achieve having the antibodies from the vaccination is shutting down the whole system from the very start.

And in fact, data show that people who have been vaccinated even when they get the disease, they don't get as sick.

And very few end up dying unless they have three or four preexisting conditions of other kind.

So, and usually we observed that what goes wrong is the prolonged, like I said inflammatory response that peaks and keeps going beyond the time that is needed for the pulmonary symptoms.

So in this case, we kind of stop the thing from even starting early on.

And this way we present... We can block all the all sets of symptoms that can develop for no particular reason.

So I would say yes, even though I think formal studies should be done to really address that.

- So more research needs to be conducted, but certainly the the early indication is that being vaccinated is protective for some of these brain effects, that may be the result of inflammation.

- Absolutely, we don't see these kind of severe presentations in the hospital, or even outside the hospital when people have COVID but have been vaccinated and they present with mild symptoms that look more like the flu, I would say.

- I wanna shift gears a little bit, and talk about the stressors that the pandemic has brought about.

But also has resulted in increase in anxiety and depression, even in people that don't have COVID.

And I'd like you to speak a little bit about that.

- Yes, has been really a tragic situation and difficult for many people.

I would like to start from the youngest, I feel that kids and adolescents the most affected.

And they are growing, they need the interactions in school for learning not just with teaching school but also learning how to be with other people, social interaction, they need to be with their friends and start dating.

And this pandemic has at least stopped their lives.

So I feel this has been really, really hard for young people and young adults who are alone and unable to achieve their goals, even college graduates they didn't have regular graduations.

It's harder to get into the job market with the remote work.

And so a lot of anxiety related to the uncertainty and the isolation and the actual loss of years at this point of social interactions.

- Yeah, if you think about a young person, a significant percentage of their life has been spent during the pandemic.

For the people like us, a couple years is a smaller percentage of our whole life it still affects us.

But for a four-year-old or a 14-year-old, or a 20-year-old it's a significant percentage of their life during the time of the pandemic.

- Yeah, it's been definitely very difficult, and has been difficult for some families many families that are happy to be together.

But there are also many families that have difficult situations at home, and being confined in a space where there are issues at home like domestic violence, or drug abuse or people who are sick and not having been able to have the support of the outside community, has exacerbated many of these conditions.

So that's another factor of the pandemic.

Many people who have difficult situations at home rely on the support of other pieces in their community not just the doctor.

And this has been missing and they have been sort of locked in, in these difficult situations.

- Let me ask you, what guidance would you give to parents of young children who have been living their life with the pandemic?

What do you suggest to parents?

- Well, it's hard because you need to be careful.

So you don't want to expose the kids as much to friends that you don't know if they are safe to be with.

And I guess what we have been all relying on these videos like today.

But I think they have saved in a way, our ability to stay connected with family and friends even the ones that are far.

So that's one thing that could be done, and I'm sure many families are doing this already.

Another thing is that I would try not to burn the youngest with my own anxiety if I was a parent.

And so try to be reassuring and show your strength and confidence in the future, and have an optimist take outlook for children.

I guess we have to do that for our children no matter what the situation is at home all the time.

And sometimes is hard to keep calm and show them the positive side of things.

- I think that's very good advice.

And I would add on that, that if you are concerned about your child or yourself, don't suffer in silence seek help for yourself, or for your child.

- Absolutely, that's fundamental.

I think one thing that this pandemic can teach us is that it's not anything to be ashamed of, when you need help.

- Maura, I wanna thank you for the work that you've been doing and the work that you're continuing to do.

And thank you for us today to share your research and knowledge about this important topic, thank you.

- My pleasure, thank you very much for having me.

(gentle music) - The pandemic has affected all of us.

If you are experiencing anxiety or depression, as a result of the stress of the pandemic, or as a result of COVID, don't suffer in silence, seek help.

Remember with help, there is hope.

(gentle music) Do not suffer in silence, with help, there is hope.

This program is brought to you in part by the American Psychiatric Association Foundation, The Bank of America Charitable Gift Fund, and The John and Polly Sparks Foundation.

Remember with help, there is hope.

(gentle music)